DESCRIPTION: The aim of the proposed studies is to identify the role of the female sex hormones relaxin and estrogen in the etiopathogenesis of TMJ disease in women. A role for estrogen in TMDs has been proposed, but little conclusive evidence to support this theory is available, and the potential role of other female sex hormones in TMDs has not been examined. Of particular interest is relaxin, which is found systemically only in cycling and pregnant women and which causes pelvic joint hypermobility. Relaxin modulates the remodeling of uterine and cervical tissues during the menstrual cycle and pregnancy. It also induces the expression of the MMPs and decreases the synthesis of TIMPs and type I collagen in dermal fibroblasts. The preliminary studies demonstrated that relaxin increases the expression of collagenase and stromalysin in cultured TMJ disc and ligament cells, but not in synoviocytes, suggesting that the disc and ligament cells may be specific target sites for the matrix-degradative effects of relaxin effects that are potentiated by prior exposure of these cells to beta estradiol. The proposed studies will test the hypothesis that relaxin and estrogen cause TMJ disease in women by increasing the expression of MMPs and decreasing that of TIMPs and collagen in joint disc and ligament cells. The specific aims are: (1) Evaluate the dose-dependent and temporal modulation of MMPs, TIMPs and type I collagen by relaxin in unprimed and estrogen-primed rabbit TMJ disc and ligament cells in culture; (2) Localize relaxin-binding sites in the unprimed and estrogen-primed rabbit TMJ and determine the relaxin-binding characteristics of TMJ disc and ligament cells; (3) Determine the proportion of systemic relaxin that accesses the estrogen-primed and arthritic rabbits; (4) Examine the effects of relaxin and estrogen on the loss of disc collagen and glycosaminoglycans in tissue explants in vivo, and evaluate the relative contributions of matrix synthesis and degradation to the net loss of disc matrices.